Influenza virus is one of the most infective viruses that cause acute respiratory diseases, and in severe instances, cause herd infection or pandemic over the world, particularly giving rise to serious respiratory symptoms in children, the aged, patients with cardiopulmonary diseases, and the like (see Hien, T. T. et al. N. Eng. J. Med., 350, 1179, 2004). Influenza virus is a genus of the Orthomyxovirus and has three types, that is, A, B, and C. Among them, particularly A and B types routinely spread in people.
Virus surface antigens produce an antigenic variation by their same subtype to generate new antigenic variants every year. Particularly, among influenza viruses, avian influenza virus, which is still a threat, undergoes an antigenic shift to infect various kinds of birds such as chickens, turkeys, ducks, wild birds, and the like. Avian influenza virus spreads so quickly that once a chicken is infected, 80% or more of the chickens are killed. Avian influenza virus which poses the most damage and threat to the poultry industry over the world causes viral diseases, and this pervasive effect is not just limited to the poultry industry. It has been reported that avian influenza virus can infect humans, which causes diseases to spread among humans (see Gubareva, L. V. et al. Lancet. 355, 2000).
In order to prevent and treat the influenza virus infection, consideration may be made to inhibit the absorption in epithelial cells, the invasion into cells, the transcription or replication of genes, the synthesis of proteins, or the release from cells, each having been the focus of the antiviral studies.
To treat diseases caused by influenza virus, four substances, that is, Amatadine, Rimatadine, Zanamivir, and Oseltamivir have been used with the approval of the Food and Drug Administration (FDA). Among these, Amatadine and Rimatadine are M2 inhibitors, which have antiviral effects by blocking an ion channel of a membrane protein, particularly M2 protein that is essential to the proliferation of virus, and inhibiting the uncoating of the virus, but they are only effective against influenza A virus. Also, it is reported that some viral become more tolerant and resistant to the inhibitors as a consequence of being used over 40 years, and severe side effects occur in the nervous system and stomach (see Bantia, S. et al. Antiviral Research 69, 39, 2006). Since 1999, as new drugs for treating virus infection, Zanamivir and Oseltamivir have been used, which play an important role in proliferation of virus, have a low prevalence of tolerance, and inhibit neuraminidases being stably present in both influenza A and B viruses (see Zhang, J. et al. Bioorg. Med. Chem. Lett. 16, 3009, 2006).
However, Zanamivir has an advantage of high antiviral effects but is disadvantageous in low bioavailability and quick release from the kidney (see Ryan, D. M. et al. Antimicrob. Agents Chemother., 39, 2583, 1995), and Oseltamivir causes severe vomiting.
As mentioned above, the known antiviral agents have serious side effects and require considerable caution in their application. Also, the development effects of vaccines are low when the vaccine virus is not matched to circulating viruses. Accordingly, there is an increasing need for a new influenza antiviral agent with excellent infection inhibition and stability. Also, there is a need to develop a new substance exhibiting good antiviral effects in the whole animal for the substantial treatment of animals infected with an influenza virus.
The present inventors have endeavored to satisfy such a need and found that a complex comprising a curcuminoid-based compound, or a plant extract comprising the compound or a fraction thereof; and stevioside, or a plant extract comprising the stevioside or a fraction thereof has a very superior virucidal effect and an excellent effect of inhibiting cell degeneration against an influenza virus, and can effectively treat a subject infected with an influenza virus even by just a small amount.